Gonadotropin-releasing hormone (GnRH) is a peptide of 10 amino acids and is also known as luteinizing-hormone releasing hormone (LHRH). Gonadotropin-releasing hormone is produced in the hypothalamus, and is responsible for the release of follicle-stimulating hormone and luteinizing hormone from the pituitary gland. Gonadotropin-releasing hormone is released from neurons in the hypothalamus, and plays a role in the complex regulation of follicle-stimulating hormone and luteinizing hormone release. Follicle-stimulating hormone and luteinizing hormone, in combination, regulate the functioning of the gonads to produce testosterone in the testes and progesterone and estrogen in the ovaries, and regulate the production and maturation of gametes. For example, follicle-stimulating hormone stimulates the growth and recruitment of immature ovarian follicles in the ovary, and luteinizing hormone triggers ovulation.
Gonadotropin-releasing hormone has been isolated and characterized as a decapeptide. Synthetic forms of gonadotropin-releasing hormone are available and modifications of the decapeptide structure of gonadotropin-releasing hormone have led to multiple gonadotropin-releasing hormone analogs that either stimulate (e.g., gonadotropin-releasing hormone agonists) or suppress (e.g., gonadotropin-releasing hormone antagonists) the release of the gonadotropins, such as luteinizing hormone and follicle-stimulating hormone.
It is important to commercial swine production to maximize reproductive efficiency to make swine production more profitable. There has been heavy reliance on daily heat detection of individual female swine with the associated labor costs devoted to manual detection of heat in the female swine based on daily checks of gilts or sows to achieve the best results with, for example, artificial insemination. Heat detection using labor intensive methods, such as daily checks, increases the probability of success with artificial insemination. Thus, devoting time, manual labor, and materials costs to daily checks for heat detection is necessary because it is difficult to predict the time of heat and ovulation (i.e., in order to determine the best time for insemination) without using methods requiring a daily regimen for monitoring heat detection. Accordingly, compositions are needed to optimize the success of insemination of animals, to reduce or eliminate the need for heat detection, to reduce the labor costs, and to increase the profitability of swine production.
Applicants have discovered a gonadotropin-releasing hormone composition in a gel useful for controlling the time of ovulation via hormone administration, and that can eliminate breeding based on estrus detection and allow a swine to receive only one or two inseminations for optimal fertility and optimal cost expenditure. Improved manufacturing processes are needed to prepare larger, uniform commercial batch sizes of this GnRH-containing composition for synchronizing the time of insemination in an animal. Applicants have discovered methods of preparing such a GnRH-containing gel composition that result in increased uniformity of the composition.